The purpose of this research project is to investigate the role of retinoids and specific retinoid-binding proteins in ocular tissues. In studies on the vitiligo mouse model of retinal degeneration we found that although the levels of interphotoreceptor retinoid-binding protein (IRBP) are elevated above normal levels, there is a strikingly abnormal distribution of the protein that could interfere with its normal function in the visual cycle of rhodopsin. Instead of being completely translocated into the outer segment interphotoreceptor matrix where it is required for rapid rhodopsin regeneration, IRBP in the mutant eye remains in the interphotoreceptor matrix of the inner segments. In confirmation of the essential role of IRBP in the visual cycle, it was found that the vitiligo mutant at 4 weeks of age demonstrated a marked reduction in the capacity to regenerate rhodopsin as compared with normal mice. In further studies of this mouse mutant, we have found that retinoic acid levels in mutant eyes are elevated 2.5 fold above normal and that 9-cis retinoic acid was readily detectable in mutant eyes, but not in controls. Since retinoic acid is a potent mediator of several biologic processes through control of the transcriptional properties of the RAR and RXR nuclear receptor families, elevation of retinoic acid and its metabolites in the mutant mouse eye could exert profound effects on other metabolic pathways, possibly contributing to the retinal degeneration observed in the mutant. The potential relevance of Drosophila retinoid- and fatty acid- binding glycoprotein (RFABG), expressed in the Semper (cone) cells of the fly compound eye, to retinoid processing in the eye was demonstrated by studies comparing the expression of this protein in retinoid-deprived flies with that in retinoid replete flies. Both RFABG protein and message were reduced to negligible levels in retinoid-deprived flies and retinoic acid supplementation restored both gene and protein expression to normal levels.